Recently, there have been attempts to restore damaged tissues through in vitro production of a part of said tissues, and various studies have been done in the field of tissue engineering. Tissue engineering is an application science which involves understanding the structure-function relationship in tissues based on the principles of life science and biotechnology and further developing biological substitutes for transplant into the human bodies to maintain, enhance or restore the functions of the human bodies. As it is recognized that there is a need for development of artificial organs or regeneration of tissues by using tissue engineering, many studies have been done on the techniques for attaching desired cells to different natural or synthetic polymer materials and implanting the cell-polymer composite in the body to reproduce tissues or organs.
The ideal polymer scaffold is a so-called porous scaffold that consists of a nontoxic material having biocompatibility for not causing blood coagulation or inflammation after implantation. In addition, this scaffold has excellent mechanical properties to support the growth of cells. For purposes of this application, the term “mechanical” may be defined as “structural”. Moreover, in its form, this scaffold permits good adhesion of cells as well as sufficient space between cells to allow cells to access oxygen or nutrients through diffusion of body fluid and to form new blood vessels actively, which results in successful cell growth and differentiation. Furthermore, cells are generally cultured on a two-dimensional surface, but a three-dimensional scaffold is required to culture cells to become tissues or organs. These three-dimensional scaffolds are preferable to permit a number of pores that may adhere cells and also include an open structure for supplying nutrients necessary for cell growth and secreting waste products from the cells.
Since the polyvinyl alcohol (PVA) scaffolds are non-toxic with good biocompatibility and can be easily prepared, they are used in wound dressing, contact lenses, and drug delivery systems, and many studies have been done in which scaffolds are used for biomaterials based on their strong mechanical and physical properties. In particular, the PVA scaffold contains a number of micropores capable of taking up a large amount of water, while exhibiting low substance-permeability. Therefore, under a weight load, the PVA scaffold causes the gel to excrete a liquid, which acts as a lubricant in the space between the bones, and the PVA scaffold has a surface structure similar to that of real cartilage and high water content. Accordingly, the PVA scaffold is particularly suitable as an artificial transplant material of cartilage.
As disclosed above, the PVA scaffold can be useful as a polymer scaffold material such as artificial cartilage material in the tissue engineering field. Therefore, it is required to have a sufficient mechanical strength to maintain its structure during normal usage as a scaffold, and to easily form a porous structure to help in regenerating tissues.
Much research has been done on the methods for ensuring the mechanical strength of the PVA scaffold, and thus a method has been established to provide the strength by physically or chemically crosslinking PVA. While the chemical method may cause toxicity in vivo due to a chemical crosslinking agent or an initiator, the physical crosslinking method is preferred to impart an appropriate strength to the PVA scaffold without adverse effects such as toxicity. The representative examples include a radiation method, a freeze/thaw method, or the like.
Meanwhile, the conventional method for providing porosity in the PVA scaffold includes the solvent-casting and particle-leaching technique which comprises mixing water-soluble polymers, sugars, salts, etc. to form a scaffold, and then dissolving these solutes in water to form pores. However, the water-soluble polymer can produce pores, but often forms a hydrogen bond with the OH-group of PVA to change the properties of the PVA. Sugars or salts such as NaCl temporarily increase the viscosity of PVA in the preparation of PVA scaffolds, making the preparation process almost impossible. Moreover, all of these substances are difficult to remove after formation of pores, and the removal becomes more difficult when the pores remain deep inside the PVA scaffolds. Due to difficulty in removing the remaining pore-forming agent, the time required to remove the pore-forming agent after crosslinking is at least 5 days, causing inefficiency in the preparation work. In addition, these pore-forming agents only form pores in the PVA scaffolds, but do not permit control of the pore size and the porosity within a specific range.